Anatomy Ch 18 Endocrine

• Endocrine:
• 1. Hormones: chemical messeners that enter the blood stream to get to target tissue
• 2. Distance: far from site of release - binds to receptors on target cells
• 3. Target cells: many cells throughout body
• 4. Time: slower
• 5. Duration: longer

• Nervous
• 1. Neurotransmitters - nerve fibers (action potential) causes neurotransmitters to be released
• 2. Distance: close - binds to receptors in postsynaptic cleft
• 3. Cells: Muscle, gland, and other neurons
• 4. Time: quick
• 5. Duration: Brief

• Hormone - (to excite or get moving) chemical messengers
• -made my endocrine glands or organs
• -enters interstitial fluid around cell
• -enters blood and it trans ported to target organ
• -acts upon target organ

• Endocrine system - all the endocrine glands and cells in the body
• glands:
• -pituitary
• -thyroid
• -parathyroid
• -adrenal
• -pineal

• Structures that have endocrine cells:
• -hypothalamus
• -thymus
• -pancreas
• -ovaries
• -testes
• -kidneys
• -stomach
• -liver
• -small intestine
• -skin
• -heart
• -adipose tissue
• -placenta

• Hormone receptors - receptors on target cell that are specific to only one hormone.
• -made of either protein or glycoprotein
• -found on the cell membrane OR in the cytoplasm of the cell

Hormone regulation - target cells have 2,000 to 10,000 receptors for particular hormone - can change based on relative concentration of circulating hormone over time

Down regulation - if hormone present in excess - number of receptors on target cell can decrease - make target cell less sensitive to hormone

Up regulation - if hormone deficit then more receptors are added - cell is more sensitive to hormone

Circulating Hormone - enters the blood stream to get to target cell - most endocrine hormones are circulating

• Local Hormone - act on neighboring cells or cell that produced them (2 types)
• 1. Paracrine - neighboring
• 2. Autocrine - cell that secreted it

No - local hormones stay in the interstitial fluid

Paracrine - local hormones that act on neighboring cells

Autocrine - local hormones that act on cell that secreted it

Both circulating and local hormones are released into the interstitial fluid surrounding the cell. From there the circulating hormone diffuse into blood capillaries. Local hormones don't leave the interstitial fluid - they act on the local cells

• Hormones divided into two major classes:
• Lipid-soluble hormones are hydophobic - they are friendly with lipids and are able to diffuse through the plasma membrane of the target cell - receptors are in the cytosol or nucleus

Water-soluble hormones are hydrophillic - don't play well with lipids and are not able to enter the target cell - receptors are in the plasma membrane of target cell

Lipid- soluble hormones (being hydrophobic) are not able to circulate in the watery blood plasma so they need to be attached to a transport protein - makes them temporarily water soluble

• Lipid-soluble hormones:
• 1. Steroid hormones - derived from cholesterol - unique R group attached to four ring structure
• 2. Thyroid hormones - T₃ and T₄ -(T₄ = thyroxine)
• --iodine attached to tyrosine (lipid soluble amino acid)
• 3. Nitric Oxide (NO) -gas - both a hormone and a neurotransmitter

• Water-soluble hormones
• 1. Amine hormsone - amino acid with COOH removed - retain amio group -NH³⁺
• **Catecholamines - EPI, NOR, DOPA synthesized from modified a.a tyrosine

• 2. Peptide Hormone (3-49 a.a.) &
• Protein Hormones (50-200 a.a)
• -ADH, GH, insulin, oxytosin
• -if attached to carb = glycoprotein hormone (LH, FSH)

• 3. Eicosanoid - derived from arachidonic acid (20 carbon fatty acid)
• -PGs and leukotrienes

Most steroid hormones are derived from cholesterol

• Cholesterol is a lipid that is only found in animal tissue
• -found in the lipid bilayer of plasma membranes

Eicosanoid - water-soluble hormone - mostly local but can be circulating as well

• -PGs - prostaglandins
• -leukotrienes

• Catecholamines - Amines - water- soluble
• Made by the adrenal medulla - adrenal glands - above the kidneys
• 1. NOR
• 2. EPI
• 3. DOPA

• EPI & NOR are SNS "fight or flight" hormones -
• ↑ HR, ↑ cardiac output → ↑ BP
• ↑ glycogen breakdown : make ATP
• ↑ lipid breakdown: make ATP
• broncodialation, pupil dialation

Transport proteins are made in the liver - they transport lipid-soluble hormones in the blood and release them at the target site

• Free Fraction - the amount of hormone that is not bound to a transport protein (the amount that is "free") in the bloodstream
• -the free fraction of a hormone is what causes the effect (can't bind to receptor while transporter protein is attached)

3 major functions:

1. make lipid-soluble hormones water soluble

2. Keeps the hormones from being filtered in the kidney (into urine) by increasing their size

3. stores hormones in the bloodstream - ready when needed

1. Turn protein synthesis on or off

2. alter permeability of the cell membrane (control what can get in)

3. Alter the rate of chemical reactions

4. can have multiple effects at one time

• 1. able to diffuse through the lipid bilayer
• 2. binds to hormone receptors in the nucleus (nuclear receptors)
• 3. alter gene expression - turns specific genes on or off
• - - ON - make mRNA → protein synthesized
• - - OFF - no mRNA made
• 4. mRNA leaves the nucleus, interacts with ribosome to synthesize protein → new protein act on cell's activity (causes the response initiated by the hormone)

• 1. hormone binds to receptor on cell membrane -FIRST MESSENGER
• 2. first messenger activates SECOND MESSENGER - cAMP (cyclic Adenosine MonoPhosphate)
• 3. second messenger activates (+) or inactivates (-) specific enzymes
• 4. actions occurs - inhibitory or stimulatory

• cascade effect: minute levels of hormone can cause big effects
• 1 first messenger (hormone bound to receptor) → 1000 second messengers synthesized

• Glycogen is a polysaccharide - body stores glucose in the form of glycogen in the liver and skeletal muscles
• Glycogen is made of glucose monomer linked to one another in branching chains.
• Insulin (anabolic) speeds the conversion of glucose into glycogen.

Glucagon and EPI (catabolic) accelerate the conversion of glycogen into glucose.

• Permissive Effect - a second hormone permits the primary hormone to have full effect - the second hormone is necessary for full effect and is called the permissive hormone
• - works by ↑ # of receptors for primary hormone to bind to
• -or by increasing synthesis of enzyme that primary hormone needs to have an effect

Synergistic Interactions - two different hormones interact - produces a great effect than either alone

Antagonistic Interaction - effects of 2 different hormones - less effective than either one alone

prolactin is a hormone that stimulates milk production

• in the presence of insulin, TH, and HGH there is increased milk production -
• -insulin, TH, and HGH are the permissive hormones here

-Hormone secretion from an endocrine gland requires a stimulus to occur -a trigger -

-secretion occurs in short bursts - regulation of secretion prevents overproduction or underproduction of any given hormone - most work through negative feedback systems.

• -the stimulus can be:
• -1. another hormone
• -2. signals from nervous system
• -3. chemical changes in the blood

The trigger for insulin release is a rise in the blood glucose level (hyperglycemia). The hyperglycemia is detected by the pancreas which stimulates the beta cells to secrete insulin.

-

• can be used to regulate hormone secretion but is rare
• - system in which the activity of a hormone produces a response that stimulates the release of more of that hormone
• - an example of this is oxytosin which is secreted by the hypothalamus and stored and secreted by the posterior pituitary.
• -Oxytocin stimulates contraction s of the smooth muscles of the uterus.
• - The contraction of the uterus stimulated the posterior pituitary to secrete more onytosin

Tropic hormone - hormone that stimulates another endocrine gland to release it's hormone

ACTH - adrencorticotropic hormone - secreted by the anterior pituitary → travels to adrenal gland → cortisol released by adrenal gland

• -Tropin is a suffix on some tropic hormones
• gonadotropins stimulate release of hormones in the gonads :
• LH - lutinizing hormone → progesterone release
• FSH - Follicle stimulating hormone → estrogen release

The hypothalamus receives input from the limbic, cortex, thalamus, RAS and sensory - integrates CNS and endocrine systems

Part of the dienchepalon

• Functions
• 1. Endocrine - releasing (+) and inhibiting (-) factors
• 2. ANS regulation
• 3. Thrist/ Hunger regulation
• 4. Temp regulation
• 5. Circadian rhythms

Hypothalamus releases to the anterior pituitary:

• RH (+) - releasing hormones
• IH (-) - inhibiting hormones

They act on the pituitary gland and cause it to release or inhibit the release of hormones (they are tropic hormones)

Hormones secreted by the hypothalamus that act on the pituitary gland:

• GHRH, GHIH - growth hormone
• TRH - Thyrotropin RH
• CRH- Corticotropin RH
• GnRH - Gonadotropin RH
• PRH, PIH - Prolactin

• synthesizes and sends to posterior pituitary for storage and release:
• 1. ADH - antidiuretic hormone
• 2. oxytosin

RH and IH do not act on the posterior pituitary - ADH and oxytosin are synthesized in the hypothalamus and travel to the posterior pituitary via the hypothalamo-hypophyseal tract

• GHRH, GHIH - Anterior Pituitary
• TRH - Anterior Pituitary
• GnRH - Anterior Pituitary
• CRH - Anterior Pituitary
• PRH, PIH - Anterior Pituitary

• ADH = Antidiuritic Hormone
• ADH increases H₂O resorption in the kidneys (concentrated urine)
• ADH is made by the hypothalamus but stored and released by the posterior pituitary
• Trigger for release:
• 1. blood electrolyte concentration
• 2. blood volume
• 3. BP
• ADH is inhibited by alcohol

• -Oxytocin increases frequency and strength of uterine contractions and promotes the letdown reflex in the breasts
• -Release is triggered by the stretching of the cervix and from sucking at the breast
• -Target organs are uterus and breasts
• - Controlled by positive feedback system - stops when the cervical stretching stops

The pituitary (also known as the hypophysis) is called the master gland

-located in the hypophyseal fossa of the sella turcica of the sphenoid bone

-the infundibulum (means funnel) is the stalk that connects the pituitary to the hypothalamus

-the anterior pituitary (adeno hypophysis) is the glandular tissue portion (made of epithelial tissue) - secretes 6 hormones

- the posterior pituitary (neuro hypophysis) is made of nervous tissue - the neurosecretory cells make ADH and oxytocin

• The hypophyseal portal system is a specialized blood supply that is a direct vascular connection between the hypothalamus to the anterior pituitary that prevents dilution of the hormones.
• hypothalamic capillaries → hypophyseal portal vein → pituitary capillaries → pituitary cell

Anterior Pituitary make 6 hormones - output is controlled by the hypothalamus R and I hormones that reach the pituitary via the hypothalamic portal system

1. GH Grown Hormone (hGH) → liver = IGF (Insulin-like Growth Factor) → cell growth and division (IGF is necessary for cell growth (hypertrophy) and cell reproduction (hyperplasia) in kids - cell maint & repair in adults)

• 2. TSH - Thyroid stimulating → thyroid = ↑ T₃ & T₄
• 3. FSH - Follicle stimulation → ovaries/ testes = (M) sperm production / (F) egg maturation & estrogen secretion

4. LH - luteinizing hormone → ovaries/ testes = (M) testosterone (F) ovulation & corpus luteum (progesterone production)

5. Prolactin → breasts = milk production

6. ACTH -AdrenoCorticoTropic hormone → Adrenal gland = cortisol (also small amts of aldosterone & androgens)

• Posterior Pituitary:
• 1. ADH - Antidiuretic Hormone → kidneys = resorption of H₂O (concentrated urine) & Vasoconstriction

2. Oxytocin → uterus & breasts = + uterine contractions & letdown reflex

GH (secreted by the Anterior Pituitary) in the blood causes secretion of IGF by the Liver (also bone, muscle, and cartilage cells)

IGF is like insulin in that it promote a.a. uptake by the cells and protein production in the cells. IGF is both anabolic and catabolic.

IGF is not like insulin in that it promotes glycogen breakdown in the liver (catabolic) -causes more glucose to enter the blood. IGF also promote lipolysis for ATP production.

IGF is opposite insulin - it causes blood glucose levels to increase because it inhibits glucose uptake by cell and it promotes glycogen breakdown in the liver which releases more glucose into the blood stream.

GH is released from somatotrophs in the anterior pituitary when GHRH is synthesized and released from the hypothalamus. GHRH is released when the blood glucose level is low, also when there are lots of a.as in the blood, or when there are low fatty acids in the blood.

• 1. GH
• 2. Insulin
• 3. Thyroid Hormone

Acromegaly and giantism are both caused by increased GH levels. Acromegaly occurs when the elevated GH occurs during adulthood. Giantism is caused by elevated GH during childhood.

TSH is secreted by Thyrotrophs in the anterior pituitiary. Secretion is controlled by the hypothalamus (TRH) and is triggers when T₃ and T₄ levels are low

TSH - Thyroid Stimulating Hormone - secreted by the anterior pituitary → act on the thyroid gland

• -Regulates T₃ and T₄ output from thyroid
• -Regulated by negative feedback via thyroid hormone blood levels

Gonads are reproductive organs.

Gonadotropins are secreted by the Gonadotrophs in the anterior pituitary. Release is triggered by GnRH from the hypothalamus.

• FSH - (M) Sperm production
• - (F) egg maturation & estrogen production

• LH - (M) Testosterone
• - (F) Ovulation & corpus luteum ( secretes progesterone)

Lactation refers to milk production and ejection from the mammary glands.

Oxytocin (released from the posterior pituitary) is responsible for release of milk form the mammary glands (letdown).

Prolactin (released by the anterior pituitary) is responsible for milk secretion by the mammary glands. (needs permissive hormones to have full effect)

AdrenoCorticoTropic Hormone

Trigger for release of cortisol from the adrenal cortex

The posterior pituitary contains pituicytes and axons from the neurosecretory cells in the hypothalamus.

A pituicyte is a glial cell similar to an astrocyte (support & protect neural cells)

The hypothalamo-hypophyseal tract is the collection of axons that travel form the hypothalamus to the posterior pituitary. ADH and oxytosin are produced by the cell bodes in the hypothalamus and travel by fast axonal transport (along the hypothalamo-hypophyseal tract) to the posterior pituitary.

The hypophyseal portal system is a special network where blood flow from capillaries to a portal vein and then into a second capillary system. It carries R and I hormones from the hypothalamus to the anterior pituitary.

• ADH targets:
• 1. Kidneys - retain & resorb water; decrease urine output

2. Sudoriferous glands - decreases output to lower water loss

3. Smooth muscle (blood vessel walls) - vasoconstriction - blood vessel walls contract - raise BP

ADH is given during cardiac arrest because it raises blood pressure which can make the heart start pumping again.

• 1. T₃ & T₄
• 2. Calcitonin

Follicular cells (around the lumen of the follicle) make TH

Parafollicular cells (in the lumen) make calcitonin

The isthmus connects the two lobes of the thyroid and is positioned anterior to the trachea

T₃ had 3 atoms of iodine attached and T₄ has 4 atoms of iodine.

They provide all the same functions, However T₃ is several time more potent than T₄ (which is produced in larger quantities)

The thyroid is the only endocrine gland that stores large amounts of the hormone it produces.

It is not critical if you miss a dose or two of thyroid medication because the thyroid stores a 100 day supply of thyroid hormone.

Thyroid hormone must bind to a transport protein called TBG - Thyroid Binding Globulin in order to enter the blood stream because it is a lipid soluble hormone.

Its free fraction is 1 % (99% is bound)

The bound hormone can not produce an effect because it cannot bind with receptors.

The colloid is the T₃ and T₄ that is collected in the lumen of the thyroid follicle. It is composed of TGB (thyroglobulin) with iodine molecules attached and them paired off. The colloid returns to the follicular cells to have the T3 and T₄ molecules removed from the TGB.

Thyroid increases the BMR (a measure of O₂ consumption under standard conditions)

Metabolism is the combined total of all catabolic and anabolic reactions in the body. Catabolism is reactions that break complex molecules down into simplier ones. Anabolism is the act of building more complex units from simplier ones.

Thyroid hormone is both anabolic and catabolic because it stimulates protein sysntesis (anabolic) and increases breakdown of carb and lipids for ATP production (catabolic)

• Thyroid Hormone:
• -increases BMR (increases ATP production)
• -Increases O₂ consumption (caloric effect)
• -Increases protein synthesis
• -Increases breakdown of carbs and lipids for ATP production
• -Increases # of beta receptors -increases HR, BP (up regulation)
• -almost all body cells have TH receptors

TH is important for normal growth because it works with insulin and GH to speed up growth, particularly in the nervous and skeletal systems.

Calcitonin (CT) is made by the parafollicular cells of the thyroid gland. It is responsible for lowering blood calcium levels by decreasing osteoclast activity and increasing osteoblast activity.

Calcitonin and PTH are both regulators of blood calcium levels. However, their functions are opposite. PTH works to increase blood calcium levels by increasing osteoclast activity and decreasing osteoblast activity.

Chief cells are the most numerous cells of the parathyroid glands. They produce PTH (also called parathormone)

There are 4 parathyroid glands. They are located on the posterior lateral lobes of the thyroid gland.

If you have low blood calcium levels the parathyroid gland secretes PTH

• PTH raises calcium by:
• -increasing osteoclast activity
• -decreasing osteoblast activity
• -increasing calcium resorption at the kidneys
• -stimulates release of calcitriol (an active form of Vit D) form the kidneys which increases absorption of calcium from food in the GI tract.

Since calcitonin and PTH have opposite effects they counteract one another.

Adrenal means "above renal". It is above and sits on the kidneys.

No, the adrenal cortex is make of glandular epithelial tissue and the adrenal medulla is make of nervous tissue.

1. Zona glomerulosa - outermost zone -produces mineralocorticoids (they affect mineral homeostasis) such as Aldosterone.

2. Zona fasciculata - middle- makes glucocorticoids (affect glucose homeostasis) such as cortisol.

3. Zona reticularis - innermost - makes androgens (male sex hormones) such as DHEA

Catecholamines are neurotransmitters that are made by the chromaffin cells of the adrenal medulla. Since the adrenal medulla is nervous tissue, the ANS exerts control over the cromaffin cells and hormone release can occur quickly.

EPI and NOR are catecholamines produced in the adrenal medulla which are used to intensify sympathetic response in other parts of the body

• Androgens are male sex hormones made in the adrenal cortex.
• In females they stimulate libido and are converted into estrogen. After menopause they are the females only source of estrogen.

• Aldosterone is a mineralocorticoid that tells the kidneys to save Na⁺ and H₂O and throw out K+
• Secretion of aldosterone is controlled by the RAA pathway (renin-angiotensin-aldosterone)
• ↓NA⁺ or ↓blood volume → ↑renin (enzyme from kidneys) → conversion to Angoitensin I (liver) → conversion to Angiotensin II (by ACE in the lungs) → release of aldosterone (adrenal cortex) → ↑Na⁺ and ↑ blood volume

Cortisol is catabolic because it stimulates protein and lipid breakdown.

Glucocorticoids have an anti-inflammatory effect in that they inhibit the WBCs that are part of inflammatory responses. They also depress the immune response which would be helpful in organ transplants to avoid tissue rejection by the immune system.

Cortisol is a sympathetic "fight or flight" hormone and it has the opposite effect of insulin.

• Addison's and Cushing's are both Adrenal gland disorders.
• Addison's - over secretion of cortisol (usually caused by tumor) causes breakdown of muscle and redistribution of body fat (moon face, buffalo hump, hanging abdomen)

• Cushing's - Too little glucocorticoids or aldosterone - caused by autoimmune that damage the adrenal cortex - lethargy, weakness, weight loss, vomiting -
• loss of aldosterone causes low sodium, low blood pressure, dehydration , cardiac arrest, "bronzed skin"

Grave's disease - hyperthyroidism - enlarged thyroid, eyes protrude (more often in females)

Goiter = enlarged thyroid gland (can be associated with hyper or hypothyroidism) can be caused by iodine deficiency.

Cretinism - Congenital hypothyroidism - newborns - must be treated or can cause mental retardation and stunted bone growth

Myxedema - hypothyroidism in adults - edema (face looks puffy) slow heart rate, dry skin and hair, general lethargy, tendency to gain weight easily

The chromaffin cells are in the adrenal medulla and secrete EPI and NOR

• EPI and NOR are released in response to stressful situations because they:
• 1. Increase HR and cardiac output which increases BP
• 2. Increase blood flow to the heart, liver, skeletal muscles, and fat (lipolysis)
• 3. Increase glycogen and lipid breakdown for ATP
• 4. Bronchodilation
• 5. pupil dilation

• Glucagon = catabolic
• Cortisol = catabolic
• EPI = catabolic
• NOR = catabolic
• Insulin = anabolic
• GH = anabolic
• TH = Both

Insulin and glucagon

In the islets (islets of Langerhans) of the pancreas the Alpha cells make glucagon and the Beta cells make insulin

The three parts of the pancreas are:

Head, Tail, and Body

If you turn yellow then your tumor is most likely at the head of the pancreas because it is blocking the bile duct and causing jaundice

Insulin is anabolic because it causes glucose and amino acid uptake into cells for the purpose of building glycogen and proteins. It lowers blood glucose by stimulating glucose uptake into cells. By enter the cells and being synthesized into glycogen the glucose level that is circulating in the blood drops

Glucagon causes glygocen in the liver and skeletal muscle to be broken down so that it can reenter the blood stream as glucose. Glucacon works to increase the blood glucose level.

EPI is a fight or flight hormone so it will increase glucagon output which will increase blood glucose levels.

ACh is a neurotransmitter that increases insulin outout

Melatonin is a peptide hormone that is made by the pineal gland (part of epithalamus in the brain). It helps the body maintain sleep (circadian rhythms). It is regulated by the amount of light on the retina. Increase in light causes a decrease in melatonin and you wake up.

Thymosin is a hormone that promotes maturation of the T cell (T lymphocytes - WBCs that destroy foreign substances)

It is made by the thymus gland which is located behind the sternum, between the lungs.

Erythropoietin is a peptide hormone that helps stimulate the production and maturation of RBCs.

Erythropoietin is make in the kidneys and travels to the bone into the red bone marrow where hemipoiesis takes place. Its release is triggered by low oxygen levels in the blood.

Renin is a hormone that is made in the kidneys. It is part of the RAA pathway (renin-angiotensin-aldosterone).

It is released into the blood when the sodium level or blood volume lever is low. It circulates in the blood until it reaches the liver when it converts angiotensinogen into angiotensin I.

The activated form of Vit D is made in the kidneys and is called calcitriol. It is a steroid hormone that increases calcium and phosphate absorption in the small intestine. Its release is triggered by low calcium in the blood.

ANP = Atrial Natriuretic Peptide

It is made in the atrium of the heart. It works to increase sodium and water loss in the kidneys (more output of water and sodium) to lower blood volume and blood pressure.

Release is triggered by an increase in atrial sretch (indicating increased blood volume or BP)

Prostoglandins and Leukotrienes are eicosinoids (water soluble local hormones). They are made by almost all cells in the body except RBCs. They are inflammatory mediators. Aspirin works by inhibiting PG synthesis. Any response that PGs would normally have - raised temperature, pain, swelling, can be counteracted by aspirin because aspirin is able to stop the PGs from being synthesized and thus stop them from raising body temperature.